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Agricultural water is commonly treated with chlorine-based disinfectants, which are impacted by water quality. Understanding how water quality influences disinfectants such as chlorine dioxide (ClO2) against pathogenic bacteria is important for creating efficacious sanitation regimens. In this study, the minimum inhibitory concentration (MIC) of ClO2 needed to achieve a 3-Log reduction against Shiga toxin-producing Escherichia coli (STEC) and Listeria monocytogenes was compared across agricultural water samples. Sterile ddH2O served as a control to compare with environmental samples from Salinas Valley, CA, and laboratory standards. To test different dosages and water qualities, stock ClO2 was diluted in 24-well plates with target concentrations of 10, 5, 2.5, and 1.25 mg/L. Well plates were inoculated with pathogens and treated with sanitizer for 5 min. Following treatment, surviving pathogens were enumerated using viable cell counts. The results demonstrate that groundwater samples had the highest water quality of the environmental samples and required the lowest concentration of disinfectant to achieve 3-Log reduction against both bacteria, with MIC between 1.4 and 2.0 mg/L. Open-source samples had lower water quality and required a higher concentration of ClO2 for 3-Log reduction, with MIC between 2.8 and 5.8 mg/L for both pathogens. There was no correlation between pH, turbidity, or conductivity/TDS and reduction for either STEC or L. monocytogenes, suggesting no individual water metric was driving reduction. A lower dosage was required to achieve 3-Log reduction against STEC, while L. monocytogenes required greater concentrations to achieve the same level of reduction. Overall, these results help guide growers in using ClO2 as a broad-spectrum disinfectant and demonstrate its efficacy in reaching 3-Log reduction across agricultural water samples.

Introduction For future success in the modern health care environment, health professions students require effective interprofessional education experiences to develop their perceptions of other professionals on the health care team. The Interprofessional Standardized Patient Experience (ISPE) is an interprofessional education activity for prelicensure health professional students in nursing, pharmacy, physical therapy, medicine, social work, and occupational therapy. Methods The ISPE involved collaboration among students to conduct a subjective interview. Students from six health care professions individually interviewed a simulated patient while being observed by students from other professions. A structured faculty-guided debriefing session followed the comprehensive interview process. Students completed a voluntary pre- and post-ISPE survey with interprofessional questions and feedback on the activity. Descriptive statistics were used to analyze individual responses. Differences in student opinions by student profession and by the number of professions present were examined using chi-square tests. Results Over 4 consecutive academic years, 1,265 students completed the ISPE, and 1,028 completed the pre- and post-ISPE surveys. Analysis of the survey responses indicated that the ISPE enhanced student awareness of the functions of an interprofessional team and increased student knowledge of the roles of different health care professions. Students rated the ISPE as a valuable experience. Differences were noted in some of the measures by profession and group size. Discussion A single ISPE had a significant impact on prelicensure students’ perceptions. The ISPE is a novel and effective approach to interprofessional education that students appreciate.

Purpose Acoustic streaming induced by applying transcranial focused ultrasound (FUS) promotes localized advective solute transport in the brain and has recently garnered research interest for drug delivery and enhancement of brain waste clearance. The acoustic streaming behavior in brain tissue is difficult to model numerically and thus warrants an in vitro examination of the effects of using different sonication parameters, in terms of frequency, intensity, and pulse duration (PD). Methods Melamine and polyvinyl alcohol (PVA) foams were used to mimic the porous brain tissue, which contains leptomeningeal fenestrations and perivascular space, while agar hydrogel was used to emulate denser neuropil. FUS was delivered to these media, which were immersed in a phosphate-buffered saline containing toluidine blue O dye, across various frequencies (400, 500, and 600 kHz; applicable to transcranial delivery) in a pulsed mode at two different spatial-peak pulse-average intensities (3 and 4 W/cm2). Results Image analysis showed that the use of 400 kHz yielded the greatest dye infiltration in melamine foam, while sonication had no impact on infiltration in the agar hydrogel due to the dominance of diffusional transport. Using a fixed spatial-peak temporal-average intensity of 0.4 W/cm2 at 400 kHz, a PD of 75 ms resulted in the greatest infiltration depth in both melamine and PVA foams among the tested range (50-150 ms). Conclusion These findings suggest the existence of a specific frequency and PD that induce greater enhancement of solute/fluid movement, which may contribute to eventual in vivo applications in promoting waste clearance from the brain.

Abstract Cerebrospinal fluid (CSF) is crucial for maintaining neuronal homeostasis, providing nutrition, and removing metabolic waste from the brain. However, the relationship between neuronal activity and CSF solute transport remains poorly understood. To investigate the effect of regional neuronal activity on CSF solute transport, Sprague–Dawley rats (all male, n = 30) under anesthesia received an intracisternal injection of a fluorescent tracer (Texas Red ovalbumin) and were subjected to unilateral electrical stimulation of a forelimb. Two groups (n = 10 each) underwent two different types of stimulation protocols for 90 min, one including intermittent 7.5-s resting periods and the other without rest. The control group was not stimulated. Compared to the control, the stimulation without resting periods led to increased transport across most of the cortical areas, including the ventricles. The group that received intermittent stimulation showed an elevated level of solute uptake in limited areas, i.e., near/within the ventricles and on the ventral brain surface. Interhemispheric differences in CSF solute transport were also found in the cortical regions that overlap with the forelimb sensorimotor area. These findings suggest that neuronal activity may trigger local and brain-wide increases in CSF solute transport, contributing to waste clearance.

Abstract Transport of interstitial fluid and solutes plays a critical role in clearing metabolic waste from the brain. Transcranial application of focused ultrasound (FUS) has been shown to promote localized cerebrospinal fluid solute uptake into the brain parenchyma; however, its effects on the transport and clearance of interstitial solutes remain unknown. We demonstrate that pulsed application of low-intensity FUS to the rat brain enhances the transport of intracortically injected fluorescent tracers (ovalbumin and high molecular-weight dextran), yielding greater parenchymal tracer volume distribution compared to the unsonicated control group (ovalbumin by 40.1% and dextran by 34.6%). Furthermore, FUS promoted the drainage of injected interstitial ovalbumin to both superficial and deep cervical lymph nodes (cLNs) ipsilateral to sonication, with 78.3% higher drainage observed in the superficial cLNs compared to the non-sonicated hemisphere. The application of FUS increased the level of solute transport visible from the dorsal brain surface, with ~ 43% greater area and ~ 19% higher fluorescence intensity than the unsonicated group, especially in the pial surface ipsilateral to sonication. The sonication did not elicit tissue-level neuronal excitation, measured by an electroencephalogram, nor did it alter the molecular weight of the tracers. These findings suggest that nonthermal transcranial FUS can enhance advective transport of interstitial solutes and their subsequent removal in a completely non-invasive fashion, offering its potential non-pharmacological utility in facilitating clearance of waste from the brain.

Abstract The efficacy of many anti-epileptic drugs, including phenytoin (PHT), is reduced by plasma protein binding (PPB) that sequesters therapeutically active drug molecules within the bloodstream. An increase in systemic dose elevates the risk of drug side effects, which demands an alternative technique to increase the unbound concentration of PHT in a region-specific manner. We present a low-intensity focused ultrasound (FUS) technique that locally enhances the efficacy of PHT by transiently disrupting its binding to albumin. We first identified the acoustic parameters that yielded the highest PHT unbinding from albumin among evaluated parameter sets using equilibrium dialysis. Then, rats with chronic mesial temporal lobe epilepsy (mTLE) received four sessions of PHT injection, each followed by 30 min of FUS delivered to the ictal region, across 2 weeks. Two additional groups of mTLE rats underwent the same procedure, but without receiving PHT or FUS. Assessment of electrographic seizure activities revealed that FUS accompanying administration of PHT effectively reduced the number and mean duration of ictal events compared to other conditions, without damaging brain tissue or the blood–brain barrier. Our results demonstrated that the FUS technique enhanced the anti-epileptic efficacy of PHT in a chronic mTLE rodent model by region-specific PPB disruption.

Abstract Efficient transport of solutes in the cerebrospinal fluid (CSF) plays a critical role in their clearance from the brain. Convective bulk flow of solutes in the CSF in the perivascular space (PVS) is considered one of the important mechanisms behind solute movement in the brain, before their ultimate drainage to the systemic lymphatic system. Acoustic pressure waves can impose radiation force on a medium in its path, inducing localized and directional fluidic flow, known as acoustic streaming. We transcranially applied low-intensity focused ultrasound (FUS) to rats that received an intracisternal injection of fluorescent CSF tracers (dextran and ovalbumin, having two different molecular weights–Mw). The sonication pulsing parameter was determined on the set that propelled the aqueous solution of toluidine blue O dye into a porous media (melamine foam) at the highest level of infiltration. Fluorescence imaging of the brain showed that application of FUS increased the uptake of ovalbumin at the sonicated plane, particularly around the ventricles, whereas the uptake of high-Mw dextran was unaffected. Numerical simulation showed that the effects of sonication were non-thermal. Sonication did not alter the animals’ behavior or disrupt the blood-brain barrier (BBB) while yielding normal brain histology. The results suggest that FUS may serve as a new non-invasive means to promote interstitial CSF solute transport in a region-specific manner without disrupting the BBB, providing potential for enhanced clearance of waste products from the brain.

The COVID-19 pandemic drastically changed how education is delivered. Many academic programs quickly transformed their curriculum to online distance learning. This rapid transition may have compromised the rigor and fidelity of these activities. The Interprofessional Standardized Patient Experience (ISPE) is an interprofessional education activity (IPE) involving a team of students from six different healthcare professions that switched to an online delivery format. This manuscript compares pharmacy students’ perceived change in interprofessional skills between the two formats. Following the ISPE, second-year pharmacy students completed the revised Interprofessional Collaborative Competencies Attainment Survey (ICCAS-R). The ICCAS-R assesses the change in interprofessional collaboration-related competencies in healthcare students before and after IPE training using a retrospective pre–post approach. For each ICCAS-R item and each delivery format (44 in-person and 51 online), paired Student’s t-test on pre- and post-ISPE scores, and Cohen’s d were calculated. Every item of the ICCAS-R was significant (p < 0.001), regardless of delivery format. Nearly all ICCAS-R items had a large effect size, and the remaining items had a medium effect size. The amount of change pre- and post-ISPE for each ICCAS-R item was calculated. Student’s t-test was used to compare the magnitude of change in interprofessional skills between the two delivery formats. Only one difference was noted between the two delivery formats—ICCAS-R item 16, which measured actively listening to interprofessional team members (p = 0.0321). When switching to an online format, the high-fidelity dimension of the ISPE was retained. The ISPE is an effective IPE activity at increasing pharmacy students’ self-perceived interprofessional collaboration skills regardless of delivery format. Even though students reported the ISPE increased their ability to actively listen to the perspectives of interprofessional team members in both formats, the magnitude of the benefit was more profound in the in-person group.

Low-intensity transcranial focused ultrasound (FUS) has gained momentum as a non-/minimally-invasive modality that facilitates the delivery of various pharmaceutical agents to the brain. With the additional ability to modulate regional brain tissue excitability, FUS is anticipated to confer potential neurotherapeutic applications whereby a deeper insight of its safety is warranted. We investigated the effects of FUS applied to the rat brain (Sprague-Dawley) shortly after an intracortical injection of fluorescent interstitial solutes, a widely used convection-enhanced delivery technique that directly (i.e., bypassing the blood–brain-barrier (BBB)) introduces drugs or interstitial tracers to the brain parenchyma. Texas Red ovalbumin (OA) and fluorescein isothiocyanate-dextran (FITC-d) were used as the interstitial tracers. Rats that did not receive sonication showed an expected interstitial distribution of OA and FITC-d around the injection site, with a wider volume distribution of OA (21.8 ± 4.0 µL) compared to that of FITC-d (7.8 ± 2.7 µL). Remarkably, nearly half of the rats exposed to the FUS developed intracerebral hemorrhaging (ICH), with a significantly higher volume of bleeding compared to a minor red blood cell extravasation from the animals that were not exposed to sonication. This finding suggests that the local cerebrovascular injury inflicted by the micro-injection was further exacerbated by the application of sonication, particularly during the acute stage of injury. Smaller tracer volume distributions and weaker fluorescent intensities, compared to the unsonicated animals, were observed for the sonicated rats that did not manifest hemorrhaging, which may indicate an enhanced degree of clearance of the injected tracers. Our results call for careful safety precautions when ultrasound sonication is desired among groups under elevated risks associated with a weakened or damaged vascular integrity.

In this work, we propose a convenient method for evaluating levels of angular jerk in augmented reality (AR) and virtual reality (VR). Jerk is a rarely analyzed metric in usability studies, although it can be measured and calculated easily with most head-worn displays and can yield highly relevant information to designers. Here, we developed and implemented a system capable of calculating and analyzing jerk in real-time based on orientation data from an off-the-shelf head-worn display. An experiment was then carried out to determine whether the presence of AR user interface annotations results in changes to users’ angular head jerk when conducting a time-pressured visual search task. Analysis of the data indicates that a decrease in jerk is significantly associated with the use of AR augmentations. As noted in the limitations section, however, the conclusions drawn from this work should be limited, as this analysis method is novel in the VR/AR space and because of methodological limitations that limited the reliability of the jerk data. The work presented herein considerably facilitates the use of jerk as a quick component measure of usability and serves as an initial point off which future research involving jerk in VR and AR can be performed.

We report the synthesis of presumably a “nanoridge” from the electrospinning of a hydrophilic polymer–protein blend. The material exhibits vertical elevation from the substrate, distinct from the morphologies seen in electrospinning. It is hypothesized that the formation of the nanostructured ridges is due to the migration of the charged protein to the apex through a highly polarized electric field in electrospinning conditions. In this study, we assessed the polyvinyl alcohol–egg albumin (PVA–EA) system in a solvent comprising of water, formic and acetic acid, together with the tip-to-collector distance (TCD) and solution flowrate. To quantify the factor effects in the surface properties of the material, a Taguchi design of experiment was used. The ridge heights observed ranged from 84.8–639.9 nm, and the material height is predominantly affected by the PVA–EA ratio and solution flow rate. The root mean square roughness was influenced by the TCD and flow rate, which has values ranging from 11.37–57.56 nm. In evaluating the sharpness of the ridge, we used the radius of curvature, where the TCD highly affects the apex sharpness. The work offers not just a likely new class of morphology, but a new perspective on the surface characterization of an electrospun material which could affect the performance of such a use in biological and physical systems.

Decades of research have highlighted the importance of optimal stimulation of cortical dopaminergic receptors, particularly the D1R receptor (D1R), for prefrontal-mediated cognition. This mechanism is particularly relevant to the cognitive deficits in schizophrenia, given the abnormalities in cortical dopamine (DA) neurotransmission and in the expression of D1R. Despite the critical need for D1R-based therapeutics, many factors have complicated their development and prevented this important therapeutic target from being adequately interrogated. Challenges include determination of the optimal level of D1R stimulation needed to improve cognitive performance, especially when D1R expression levels, affinity states, DA levels, and the resulting D1R occupancy by DA, are not clearly known in schizophrenia, and may display great interindividual and intraindividual variability related to cognitive states and other physiological variables. These directly affect the selection of the level of stimulation necessary to correct the underlying neurobiology. The optimal mechanism for stimulation is also unknown and could include partial or full agonism, biased agonism, or positive allosteric modulation. Furthermore, the development of D1R targeting drugs has been complicated by complexities in extrapolating from in vitro affinity determinations to in vivo use. Prior D1R-targeted drugs have been unsuccessful due to poor bioavailability, pharmacokinetics, and insufficient target engagement at tolerable doses. Newer drugs have recently become available, and these must be tested in the context of carefully designed paradigms that address methodological challenges. In this paper, we discuss how a better understanding of these challenges has shaped our proposed experimental design for testing a new D1R/D5R partial agonist, PF-06412562, renamed CVL-562. [ABSTRACT FROM AUTHOR]

Brain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses have uncovered reduced brain reserves and connectivity in patients with SCZ compared to typically aging individuals. These data may indicate early abnormalities of neuronal function following cyto-architectural alterations in SCZ. The current mechanistic knowledge on brain aging, epigenetic changes, and their neuropsychiatric disease association remains incomplete. With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders. It is known that environmental factors such as mode of birth, dietary habits, stress, pollution, and infections can modulate the microbiota system to regulate intrinsic neuronal activity and brain reserves through the vagus nerve and enteric nervous system. Microbiota-derived molecules can trigger continuous activation of the microglial sensome, groups of receptors and proteins that permit microglia to remodel the brain neurochemistry based on complex environmental activities. This remodeling causes aberrant brain plasticity as early as fetal developmental stages, and after the onset of first-episode psychosis. In the central nervous system, microglia, the resident immune surveillance cells, are involved in neurogenesis, phagocytosis of synapses and neurological dysfunction. Here, we review recent emerging experimental and clinical evidence regarding the gut-brain microglia axis involvement in SCZ pathology and etiology, the hypothesis of brain reserve and accelerated aging induced by dietary habits, stress, pollution, infections, and other factors. We also include in our review the possibilities and consequences of gut dysbiosis activities on microglial function and dysfunction, together with the effects of antipsychotics on the gut microbiome: therapeutic and adverse effects, role of fecal microbiota transplant and psychobiotics on microglial sensomes, brain reserves and SCZ-derived accelerated aging. We end the review with suggestions that may be applicable to the clinical setting. For example, we propose that psychobiotics might contribute to antipsychotic-induced therapeutic benefits or adverse effects, as well as reduce the aging process through the gut-brain microglia axis. Overall, we hope that this review will help increase the understanding of SCZ pathogenesis as related to chronobiology and the gut microbiome, as well as reveal new concepts that will serve as novel treatment targets for SCZ.

In recent years, glial cells have been acknowledged as key players in the pathogenesis of Alzheimer’s disease (AD), a neurodegenerative condition in which an accumulation of intracellular neurofibrillary tangles and extracellular fibrillar amyloid beta is notably observed in the central nervous system. Genome-wide association studies have shown, both in microglia and astrocytes, an increase in gene variants associated with a higher risk of developing late-onset AD. Microglia, the resident innate immune cells of the brain, and astrocytes, glial cells crucial for vascular integrity and neuronal support, both agglomerate near amyloid beta plaques and dystrophic neurites where they participate in the elimination of these harmful parenchymal elements. However, their role in AD pathogenesis has been challenging to resolve due to the highly heterogeneous nature of these cell populations, i.e., their molecular, morphological, and ultrastructural diversity, together with their ever-changing responsiveness and functions throughout the pathological course of AD. With the recent expansions in the field of glial heterogeneity through innovative advances in state-of-the-art microscopy and -omics techniques, novel concepts and questions arose, notably pertaining to how the diverse microglial and astrocytic states interact with each other and with the AD hallmarks, and how their concerted efforts/actions impact the progression of the disease. In this review, we discuss the recent advances and findings on the topic of glial heterogeneity, particularly focusing on the relationships of these cells with AD hallmarks (e.g., amyloid beta plaques, neurofibrillary tangles, synaptic loss, and dystrophic neurites) in murine models of AD pathology and post-mortem brain samples of patients with AD.

The ARIADNE Experiment, utilising a 1-ton dual-phase Liquid Argon Time Projection Chamber (LArTPC), aims to develop and mature optical readout technology for large scale LAr detectors. This paper describes the characterisation, using cosmic muons, of a Timepix3-based camera mounted on the ARIADNE detector. The raw data from the camera are natively 3D and zero suppressed, allowing for straightforward event reconstruction, and a gallery of reconstructed LAr interaction events is presented. Taking advantage of the 1.6 ns time resolution of the readout, the drift velocity of the ionised electrons in LAr was determined to be 1.608 ± 0.005 mm/μs at 0.54 kV/cm. Energy calibration and resolution were determined using through-going muons. The energy resolution was found to be approximately 11% for the presented dataset. A preliminary study of the energy deposition (dEdX) as a function of distance has also been performed for two stopping muon events, and comparison to GEANT4 simulation shows good agreement. The results presented demonstrate the capabilities of this technology, and its application is discussed in the context of the future kiloton-scale dual-phase LAr detectors that will be used in the DUNE programme.

Online courses provide students the opportunity and flexibility to attend college courses on their own schedule and within the comforts of their own home. While most enjoy the flexibility offered by this type of course delivery method and the quality between distance (online) and face-to-face courses being relatively equal, the question has been raised about the student satisfaction in online or hybrid courses (online courses containing synchronous elements). This paper seeks to explore student satisfaction toward online courses through the lens of preference to delivery method, the impact of asynchronous instruction on satisfaction and the role of rapport/ collaboration between students in an online environment. To fully understand the impact that these aspects have on student satisfaction, a survey was constructed and distributed to the entire student population of the Learning Technologies department at a public institution of higher learning in Texas. As an added dimension to the results obtained by the survey, interviews were held with a subsection of the survey participants to further explore the elements that impact their satisfaction towards online courses.